That point matters in practice.
When mitral regurgitation is secondary to ventricular disease, treating the ventricle often improves the valve leak. For that reason, the first step is usually not a valve procedure. The first step is to optimise heart failure therapy and, in selected patients, to consider cardiac resynchronisation therapy (CRT).
This case illustrates that principle well.
In secondary mitral regurgitation, the severity of the leak should be reassessed after optimal heart failure therapy and, where indicated, after CRT. In some patients, mitral regurgitation improves substantially once the ventricle is treated properly.
A clinical case
A 53-year-old man was referred for further assessment after recurrent episodes of acute pulmonary oedema. He had significant exertional dyspnoea consistent with NYHA class III symptoms.
Investigations
Echocardiography showed:
- Severe left ventricular systolic dysfunction with an ejection fraction of approximately 20%
- Moderate to severe secondary mitral regurgitation
- Severe left ventricular dilatation
His ECG showed sinus rhythm with left bundle branch block and a QRS duration of 177 ms.
Coronary angiography demonstrated normal coronary arteries. A cardiac MRI did not show major infarction or infiltrative disease. The overall picture was most consistent with non-ischaemic dilated cardiomyopathy.
Echocardiographic findings at presentation
The following echo cine loops demonstrate severe LV dysfunction and dilatation with moderate to severe secondary mitral regurgitation at the time of presentation:
Treatment and progress
Medical therapy
The patient was initiated on heart failure therapy including sacubitril/valsartan, nebivolol, and spironolactone. Uptitration was complicated by recurrent hypotension and syncope, requiring careful dose adjustment over several months.
Device therapy
A CRT-D device was implanted after six months of maximum tolerated medical therapy, given persistent symptoms, severe LV dysfunction, LBBB, and a broad QRS (177 ms).
Two months after implantation, the patient received three inappropriate shocks from the device due to rapidly conducted atrial fibrillation. He was started on amiodarone and apixaban, and appropriate device reprogramming was performed. He subsequently underwent AV node ablation to ensure reliable biventricular pacing — a key step, since the benefit of CRT depends on achieving a high percentage of biventricular capture, which can be undermined by competing AF with rapid ventricular response.
Outcome
Over the following 18 months, his clinical status improved markedly. He progressed from NYHA class III to class I, with no further hospitalisations. Alongside medical therapy and device optimisation, he also made significant lifestyle modifications.
A repeat echocardiogram showed improvement in LV systolic function, reduction in LV size, and clear improvement in the degree of secondary mitral regurgitation.
Echocardiographic findings after treatment
Before and after comparison
The side-by-side comparison below demonstrates the degree of reverse remodelling and improvement in mitral regurgitation following optimised medical therapy and CRT.
LV size
Mitral regurgitation — 4-chamber view
Mitral regurgitation — 2-chamber view
Why secondary mitral regurgitation improves with heart failure treatment
As the left ventricle dilates and remodels, the papillary muscles are displaced, the mitral annulus may enlarge, leaflet coaptation worsens, tethering forces increase, and closing forces may fall if LV systolic function is poor. The result is an incompetent valve — even though the valve tissue itself may not be the primary issue.
That is why treatment aimed at the ventricle can reduce the severity of the regurgitation.
Why GDMT matters
Guideline-directed medical therapy is central in the management of HFrEF and, by extension, in the management of secondary mitral regurgitation. When heart failure treatment is optimised, several things may occur: LV filling pressures fall, reverse remodelling occurs, LV size decreases, mitral leaflet tethering lessens, and secondary MR may become less severe.
This is why it is important not to rush to valve intervention before heart failure therapy has been optimised as far as possible.
Guideline-directed medical therapy for HFrEF — current recommendations
The following table summarises the four pillars of foundational GDMT for heart failure with reduced ejection fraction, along with selected additional therapies, based on the 2022 AHA/ACC/HFSA and 2024 ACC Expert Consensus guidelines.
| Class | Medication | Starting dose | Target dose | Key trial(s) | Recommendation |
|---|---|---|---|---|---|
| Pillar 1 ARNI / ACEi / ARB |
Sacubitril/valsartan Entresto — preferred |
24/26 mg BD | 97/103 mg BD | PARADIGM-HF | Class I |
| Enalapril if ARNI not tolerated |
2.5 mg BD | 10–20 mg BD | CONSENSUS, SOLVD | Class I | |
| Candesartan / Valsartan if ACEi not tolerated |
4–8 mg daily | 32 mg daily (C) / 160 mg BD (V) | CHARM, Val-HeFT | Class I | |
| Pillar 2 Beta-blocker |
Carvedilol | 3.125 mg BD | 25 mg BD (50 mg BD if >85 kg) |
COPERNICUS | Class I |
| Metoprolol succinate (CR/XL formulation) |
12.5–25 mg daily | 200 mg daily | MERIT-HF | Class I | |
| Bisoprolol | 1.25 mg daily | 10 mg daily | CIBIS-II | Class I | |
| Pillar 3 MRA |
Spironolactone | 12.5–25 mg daily | 25–50 mg daily | RALES | Class I |
| Eplerenone | 25 mg daily | 50 mg daily | EMPHASIS-HF, EPHESUS | Class I | |
| Pillar 4 SGLT2 inhibitor |
Dapagliflozin Forxiga |
10 mg daily | 10 mg daily | DAPA-HF | Class I |
| Empagliflozin Jardiance |
10 mg daily | 10 mg daily | EMPEROR-Reduced | Class I | |
| Additional Diuretic |
Frusemide symptom relief only |
20–40 mg daily | Lowest effective dose | — | Class I (congestion) |
| Additional Vasodilator |
Hydralazine / isosorbide dinitrate if ARNI/ACEi/ARB not tolerated |
25/20 mg TDS | 75/40 mg TDS | A-HeFT, V-HeFT | Class I (selected) |
| Additional If channel blocker |
Ivabradine if HR ≥70 on max BB |
2.5–5 mg BD | 7.5 mg BD | SHIFT | Class IIa |
| Additional sGC stimulator |
Vericiguat worsening HF on max GDMT |
2.5 mg daily | 10 mg daily | VICTORIA | Class IIb |
BD = twice daily. TDS = three times daily. ARNI = angiotensin receptor–neprilysin inhibitor. ACEi = ACE inhibitor. ARB = angiotensin receptor blocker. MRA = mineralocorticoid receptor antagonist. SGLT2i = sodium-glucose cotransporter-2 inhibitor. sGC = soluble guanylate cyclase. Doses and recommendations based on the 2022 AHA/ACC/HFSA Heart Failure Guidelines and the 2024 ACC Expert Consensus Decision Pathway for HFrEF.
Why CRT can make a major difference
In patients with HFrEF, left bundle branch block, and a wide QRS (≥150 ms), CRT can be particularly valuable. CRT may improve secondary mitral regurgitation through several mechanisms: better ventricular synchrony, more coordinated papillary muscle function, improved closing forces, reduction in LV volumes over time, and reverse remodelling with improved geometry of the mitral apparatus.
Some patients show dramatic improvement in both symptoms and MR severity after CRT. This case is a good example.
When should the valve still be considered?
This is where transcatheter edge-to-edge repair (TEER), such as MitraClip, may have an important role in carefully selected patients.
The key is patient selection — and this is where the concepts of proportionate and disproportionate MR become important.
COAPT versus MITRA-FR — what the trials taught us
The COAPT trial showed that MitraClip in patients with heart failure and significant secondary MR reduced hospitalisations and improved survival compared with medical therapy alone. In contrast, the MITRA-FR trial found no significant difference in outcomes between the intervention and medical therapy groups.
The most widely accepted explanation for this discrepancy relates to the concept of proportionate versus disproportionate MR, described by Grayburn and colleagues. COAPT enrolled patients whose MR was disproportionately severe relative to their LV size — these are patients where fixing the valve is more likely to help because the MR is contributing to the problem beyond what the ventricular disease alone would explain. MITRA-FR included more patients with proportionate MR, where the degree of MR was roughly what you would expect for the degree of LV dilatation — and in those patients, addressing the ventricle is likely more important than addressing the valve.
- Secondary mitral regurgitation is usually a ventricular problem first
- Optimise heart failure treatment before deciding on valve intervention — including all four pillars of GDMT
- Reassess MR severity after GDMT optimisation
- Consider CRT in appropriate patients with LV dysfunction, LBBB, and a broad QRS
- Some patients improve dramatically without needing immediate mitral valve intervention
- Persistent severe symptomatic secondary MR despite optimal therapy may justify referral for TEER assessment — particularly when MR is disproportionate to LV size
Frequently asked questions
Secondary mitral regurgitation (also called functional mitral regurgitation) is mitral valve leakage caused by changes in the left ventricle — enlargement, remodelling, and dysfunction — rather than a primary abnormality of the valve leaflets themselves. It is common in patients with heart failure with reduced ejection fraction.
Yes. In some patients, the severity of secondary mitral regurgitation improves substantially after optimal heart failure therapy and CRT. As the ventricle improves and reverse remodelling occurs, the tethering forces on the mitral leaflets are reduced and the valve leak may decrease significantly or even resolve.
The four foundational pillars of guideline-directed medical therapy for heart failure with reduced ejection fraction are: (1) an ARNI such as sacubitril/valsartan (or an ACE inhibitor/ARB if ARNI is not tolerated), (2) an evidence-based beta-blocker (carvedilol, bisoprolol, or metoprolol succinate), (3) a mineralocorticoid receptor antagonist (spironolactone or eplerenone), and (4) an SGLT2 inhibitor (dapagliflozin or empagliflozin). Together, these four classes have been shown to reduce the relative risk of all-cause mortality by approximately 60–70%.
Cardiac resynchronisation therapy can improve ventricular synchrony, reduce remodelling, and improve mitral valve closing mechanics. In patients with left bundle branch block and a broad QRS, CRT restores more coordinated contraction of the ventricle, which reduces the displacement of the papillary muscles and improves leaflet coaptation — leading to a reduction in mitral regurgitation.
Transcatheter edge-to-edge repair (MitraClip) may be considered in selected patients who remain symptomatic with severe secondary mitral regurgitation despite fully optimised medical therapy and, where appropriate, CRT. The best evidence for benefit comes from the COAPT trial, which enrolled patients with disproportionately severe MR relative to their LV size. Patient selection is critical — not all patients with secondary MR will benefit from valve intervention.
This concept, described by Grayburn and colleagues, helps explain when fixing secondary MR is likely to help. In proportionate MR, the severity of the leak is roughly what you would expect for the degree of LV dilatation — the ventricle is the main problem. In disproportionate MR, the leak is more severe than the degree of LV dilatation would predict — the MR itself is contributing significantly to the patient's deterioration. Patients with disproportionate MR are more likely to benefit from valve intervention such as MitraClip.
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